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Research Currents
Observational
Study Designs: Case-Control Study
A case-control study entails a comparison of prior
exposures or characteristics of ill people (cases)
with those of people at risk for the illness in
the population from which the cases arose. Generally,
the prior experience of people at risk is estimated
from observations on a sample of that population
(controls). A difference in the frequency or levels
of exposure between cases and controls– that
is, an association – may be a reflection
of a causal link.
Ideally, the cases in a case-control study would
comprise all (or a representative sample of) members
of a defined population who develop a given health
outcome during a given period of time. The population
from which cases are to be drawn may be defined
geographically, or it may be defined on the basis
of other characteristics, such as membership in
a prepaid health-care plan or an occupational group.
The identification of all newly ill people in a
defined population can be facilitated by the presence
of a reporting system, such as a cancer or malformation
registry, that seeks to accomplish this identification
for other purposes. However, in many instances
it is not feasible to identify all cases that occur
in a given population, and so often case-control
studies are based on cases identified from hospital
records, or from the records of selected providers
from whom patients had sought health care.
When the cases identified in a case-control study
are all or a sample of those that occurred in a
defined population, one can seek to achieve comparability
by choosing as controls people sampled from that
same population. Alternatively, when cases are
chosen from a narrow range of providers of health
care, controls are often chosen from other ill
people treated by these providers. However, the
choice of ill or deceased controls can give rise
to bias if the illnesses represented in the control
group are in some way associated with the exposure
of interest. For example, ill or recently deceased
people tend to have been smokers of cigarettes
more often than other people (McLaughlin et al.
1985), since smoking is associated with a variety
of causes of illness and death. Because smoking
histories of ill people overstate the cigarette
consumption of the population from which the cases
arose (even if that population cannot be defined),
studies that use ill people as controls will tend
to underestimate any negative impact of smoking
on the risk of a given disease.
Case-control studies may be of particular value
in the evaluation of the etiology of uncommon illnesses.
However, they may have difficulty in obtaining
statistically precise results if the frequency
of the exposure in the population under study is
either extremely common or extremely uncommon (Crombie
1981). Thus, only an association as strong as the
one between cigarette smoking and lung cancer could
have emerged reliably from case-control studies
of several hundred British men conducted in the
late 1940s (Doll and Hill 1950), given that well
over 90 per cent of that population were cigarette
smokers. For a very uncommon exposure – for
example, occupational exposure to a specific substance
suspected of posing a risk to health, or an infrequently
prescribed drug – barring a strong observed
association based on a large number of subjects,
even the best-designed case-control study will
usually offer no more than a suggestion of the
presence or absence of a relation with regard to
the occurrence of a given illness.
This essay has been adapted from:
Weiss NS, Case-control studies. In: Detels R, McEwen
J, Beaglehole R, and Tanaka H, eds. Oxford Textbook
of Public Health, volume 2, The Methods of Public
Health, 4th ed. New York, NY: Oxford University
Press; 2002:543-52
References
Crombie, I.K. (1981) The limitations of case-control
studies in the detection of environmental carcinogens.
Journal of Epidemiology and Community Health, 35,
281 –7.
Doll, R. and Hill, A.B. (1950). Smoking and carcinoma
of the lung. British Medical Journal, 2, 739-48.
McLaughlin, J.K., Blot, W.J., Mehl, E.S., et al
(1985). Problems in the use of dead controls in
case-control studies. II. Effect of excluding certain
causes of death. American Journal of Epidemiology,
122, 485-94.
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